A 64-year-old man comes to the emergency department due to fever, anorexia, and nausea. He recently immigrated to the United States to live with his son. Several weeks ago, on routine testing, the patient was found to have a positive purified protein derivative test. He had no respiratory symptoms, and a chest x-ray was unremarkable. A month ago, he started isoniazid therapy with pyridoxine supplementation. Currently, temperature is 38.3 C (100.9 F). On physical examination, there is mild abdominal discomfort. Laboratory studies are pending. Which of the following is the most likely cause of this patient's current symptoms?

Question

A 64-year-old man comes to the emergency department due to fever, anorexia, and nausea.  He recently immigrated to the United States to live with his son.  Several weeks ago, on routine testing, the patient was found to have a positive purified protein derivative test.  He had no respiratory symptoms, and a chest x-ray was unremarkable.  A month ago, he started isoniazid therapy with pyridoxine supplementation.  Currently, temperature is 38.3 C (100.9 F).  On physical examination, there is mild abdominal discomfort.  Laboratory studies are pending.  Which of the following is the most likely cause of this patient's current symptoms?

Quizplus · Accepted Answer

This patient with latent tuberculosis infection (positive tuberculin skin test, no symptoms, unremarkable chest x-ray) was started on isoniazid (INH) therapy and now has fever, anorexia, and nausea. INH is directly hepatotoxic. In 10%-20% of patients, it causes acute, mild hepatic dysfunction, characterized by transient increases in serum aminotransferases (AST/SGOT, ALT/SGPT). This adverse effect usually occurs during the first 4-6 months of treatment, and, in most cases, liver function tests return to baseline with continued INH therapy. In rare instances (<1%), frank hepatitis (similar to viral hepatitis with fever, anorexia, nausea, jaundice) can occur (as seen in this patient) and sometimes evolves into a severe form with progressive liver dysfunction and death. (Choice A) Factitious disorder is the intentional falsification or inducement of symptoms with the goal of assuming the sick role. It is unlikely in this patient, who should be evaluated for INH hepatotoxicity. (Choice B) Nonsteroidal anti-inflammatory drugs can cause gastric mucosal damage by inhibiting gastric prostaglandin production. (Choice D) Peripheral neuropathy is also a potential side effect of INH therapy if simultaneous pyridoxine is not administered. However, peripheral neuropathy would not cause the above symptoms. (Choice E) Serum sickness drug hypersensitivity generally causes fever, urticaria, arthralgias, proteinuria, and lymphadenopathy 5-10 days after exposure to the drug (antigen). This patient does not have arthralgias or skin findings. Educational objective: Isoniazid can be directly hepatotoxic, causing acute, mild hepatic dysfunction in 10%-20% of patients and frank hepatitis (fever, anorexia, and nausea, sometimes progressing to hepatic failure) in a small percentage of patients.

A 64-Year-Old Man Comes to the Emergency Department Due to Fever